A publication entitled "Two dithiacyclohexadiene Polyacetylenes from Chaenactis douglasii and Eriophvllum lanatum", Norton, R.A.; Finlayson, A.J.; Towers, G.H.N.; Phytochemistry, 24(2), 356-7 (1985) discloses two dithiapolyacetylenes isolated from the roots of C. douglasii and from the plant roots as well as root cultures of E. lanatum. The two dithiapolyacetylenes have the respective chemical names 3 - (1- -propynyl) 6 (5-hexen-3-yn-1-ynyl)1,2-dithiacyclohexa-3,5- diene and 3 (pent-3-yn-1-ynyl) 6 (3-buten-1-ynyl)-1,2- dithiacyclohexa-3,5-diene. The trivial names Thiarubrine A and Thiarubrine B, respectively, have been given to these compounds.
Another publication entitled "Production of Antibiotic Thiarubrines by a Crown Gall Tumor Line of Chaenactis douglasii", Cosio, E.G.; Norton, R.A.; Towers, E.; Finlayson, A.J.; Rodriguez, E.; Towers, G.H.N.; J. Plant Physiol., 124 (1-2), 155-64 (1986) discloses dithiacyclohexadiene polyacetylenes which display considerable antimicrobial activity. A culture that accumulates these compounds was obtained by selection of red-colored areas from crown gall tumor cultures of Chaenactis douglasii. The tumors were induced by Agrobacterium tumefaciens strain A277. The main acetylenic products found were two Thiarubrines, A and B, and their corresponding thiophenes. Average yields of thiarubrines and thiophenes were 2.5 and 0.24 mg/.g dry weight, respectively, which are similar to the values seen in intact plants. The products accumulate in intercellular spaces arranged around a core of vascular tissue, forming red nodules of varying size. The structures crudely resemble the tissue organization of the roots of this plant, the only organ where these compounds accumulate. Formation of rootlets, however, did not take place at any stage during the growth of the tumors. Apparently, accumulation of these polyacetylenes by the tumor line is not a direct result of cellular transformation but a secondary effect of the existing degree of tissue differentiation.
The publication "Thiarubrine Accumulation in Hairy Root Cultures of Chaenactis douglasii", Constabel, C.P.; Towers, G.H.N.; J. Plant Physiol., 133(1), 67-72 (1988) discloses hairy root cultures of C. douglasii established using Agrobacterium rhizogenes strain TR7. One culture line accumulated twice the levels of the antifungal polyines, Thiarubrines A and B, compared to non-transformed control root cultures, while maintaining rapid growth. The combination of fast growth and high thiarubrine accumulation could not be duplicated in controls by adding exogenous NAA to the culture medium. Hairy root cultures also produced less Thiarubrine B relative to Thiarubrine A compared to controls.
A publication entitled "Antiviral Properties of Thiarubrine A, a Naturally Occurring Polyine", Hudson J.B.; Graham E.A.; Fong R; Finlayson A.J., Towers G.H.N.; Planta Med 0(1), 1986, 51-54 relates to the naturally occurring polyine, Thiarubrine A. It was evaluated for its antiviral properties in the presence and absence of long wave UV radiation (UV-A). Four viruses and a mammalian cell line were used as targets. The two mammalian viruses, murine cytomegalovirus and Sindbis virus, both of which possess membranes, were extremely sensitive to the compound, but only in the presence of UV-A radiation. The bacteriophage T4 was slightly affected in UV-A only, whereas the bacteriophage M13 was completely unaffected. Thus Thiarubrine A is photoactive against membrane containing viruses. In contrast mouse cells were moderately sensitive to the compound in the presence of UV-A, and somewhat less sensitive in the dark.
Thiarubrine A is also discussed in "Antibiotic Properties of Thiarubrine A a Naturally Occurring Dithiacyclohexadiene Polyine", Towers G.H.N.; Abramowski Z; Finlayson A.J.; Zucconi A; Planta Med 0 (3), 1985, 225-229. Thiarubrine A, a dithiacyclohexadiene polyine from the roots of Chaenactis douglassii, is disclosed as exhibiting strong antifungal activity towards Candida albicans and Aspergillus fumigatus at concentrations comparable to those of amphotericin B. It also exhibits cytotoxic activity towards Escherichia coli, Bacillus subtilis and Hycobacteria sp. and the nematode Coenorhabditis elogans. A thiophene derived from thiarubrine A was phototoxic, requiring UV-A light for biological activity. The effects of Thiarubrine A, thiophene A and alpha-terthienyl on the above organisms, as well as on CHO cells, were compared.
Polyacetylene groups and thiophenes are disclosed in "comparison of the antiviral effects of naturally occurring thiophenes and polyacetylenes", Hudson J. B.; Graham E.A.; Chan G; Finlayson A.J.; Towers G.H.N.; Planta Med 0 (6], 1986 (Recd. 1987), 453-457. Five naturally 35 occurring compounds, containing various thiophene and polyacetylene groups, were compared with respect to their phototoxic activities against two animal viruses, murine cytomegalovirus and Sindbis virus, both of which possess membranes. Alpha-Terthienyl was extremely toxic to both viruses, but only in the presence of long wave ultraviolet radiation. The order of potency was alpha-terthienyl thiarubrine-A &gt; phenylheptatriyne &gt; ACBP-thiophene &gt; thiophene-A (hydrolysis product of thiarubrine A). The murine-CMV, which had been inactivated by any of these compounds, was still capable of penetrating cultured mouse cells efficiently and reaching the cell nucleus, the normal site of virus replication. The results are discussed in terms of possible mechanisms of action of phototoxic thiophenes and polyacetylenes.
Canadian Patent No. 1,169,767, issued Jun. 26, 1984, Towers et al., discloses cercaricidal compositions containing naturally occurring conjugated polyacetylenes and method for controlling cercariae using the same.
Canadian Patent No. 1,172,460, granted Aug. 14, 1984, Towers et al., discloses a method for controlling weeds using naturally occurring conjugated polyacetylenes.
Canadian Patent No. 1,173,743, granted Sep. 4, 1984, Towers et al., discloses a method for controlling pests using naturally occurring conjugated polyacetylenes.